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Dissecting the interaction between COVID-19 and diabetes mellitus.
Chee, YJ, Tan, SK, Yeoh, E
Journal of diabetes investigation. 2020;11(5):1104-1114
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Several countries have reported higher death rates and more severe cases of covid-19 amongst individuals with chronic diseases such as type 2 diabetes. This review of 100 papers aimed to investigate the interconnecting factors which may contribute to poorer prognosis in individuals with covid-19 and type 2 diabetes. Although the evidence suggests that patients with type 2 diabetes have poorer outcomes after contracting covid-19, they are not more susceptible to infection. The paper reported that mechanisms which may increase severity in type 2 diabetics are abnormal immune function, increased susceptibility to inflammation, the increased adherence of the virus to target cells and reduced ability to fight infection. It is important to manage blood sugars when suffering from covid-19. The paper reviewed the use of several medications such as metformin, dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide-1 agonists and insulin in the context of individuals suffering from covid-19, with insulin being the treatment of choice in the acutely ill patient. Current treatments of covid-19 were also reviewed such as chloroquine and hydroxychloroquine, Lopinavir-ritonavir, IL-6 receptor agonists, type 1 interferon and remdesivir. It was concluded that clinicians should be aware of the risks in patients with type 2 diabetes and covid-19. However as new data is made available, the chronic and long-term implications will become clearer. This study could be used by health care professionals to ensure that patients with type 2 diabetes do everything they can to avoid covid-19 infection and that if contracted these patients are closely monitored for severe disease.
Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.
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Genomics in Personalized Nutrition: Can You "Eat for Your Genes"?
Mullins, VA, Bresette, W, Johnstone, L, Hallmark, B, Chilton, FH
Nutrients. 2020;12(10)
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Genetics may have a huge influence on how nutrients are processed within the body, challenging the one-size-fits-all dietary approach and highlighting the possible need for personalised nutrition based on genetics. There are a growing number of companies that offer genetic nutritional testing, however the science behind this is still in its infancy. This review of 130 papers aimed to discuss the role of genetics in nutrition and the possibility for precision nutrition. The paper stated that dietary components, especially those found in the modern Western diet (WD), may detrimentally interact with genetics. Overconsumption of certain nutrients, changes in nutrient exposure throughout history and the ability of certain nutrients to make small genetic changes are all ways that genetics and diet can interact. Therefore, understanding how an individual’s genetics have been and continue to be affected by diet may ensure effective nutrition recommendations. Ethical implications should be considered prior to testing and whether results will motivate or dissuade an individual to make dietary changes assessed. It was concluded that personalised nutrition recommendations in the future will rely upon understanding an individual’s genetics, however current research has a limited understanding of the numerous diet-genetic interactions. This paper could be used by healthcare professionals to evaluate the need for genetic testing to make personalised recommendations.
Abstract
Genome-wide single nucleotide polymorphism (SNP) data are now quickly and inexpensively acquired, raising the prospect of creating personalized dietary recommendations based on an individual's genetic variability at multiple SNPs. However, relatively little is known about most specific gene-diet interactions, and many molecular and clinical phenotypes of interest (e.g., body mass index [BMI]) involve multiple genes. In this review, we discuss direct to consumer genetic testing (DTC-GT) and the current potential for precision nutrition based on an individual's genetic data. We review important issues such as dietary exposure and genetic architecture addressing the concepts of penetrance, pleiotropy, epistasis, polygenicity, and epigenetics. More specifically, we discuss how they complicate using genotypic data to predict phenotypes as well as response to dietary interventions. Then, several examples (including caffeine sensitivity, alcohol dependence, non-alcoholic fatty liver disease, obesity/appetite, cardiovascular, Alzheimer's disease, folate metabolism, long-chain fatty acid biosynthesis, and vitamin D metabolism) are provided illustrating how genotypic information could be used to inform nutritional recommendations. We conclude by examining ethical considerations and practical applications for using genetic information to inform dietary choices and the future role genetics may play in adopting changes beyond population-wide healthy eating guidelines.
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Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease.
Lombardi, R, Iuculano, F, Pallini, G, Fargion, S, Fracanzani, AL
International journal of molecular sciences. 2020;21(22)
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Non-alcoholic fatty liver disease (NAFLD) and heart disease are influenced by diet and genetics. NAFLD cannot be managed with drugs and so lifestyle modification is the main recommendation, which is also advised in heart disease. The aim of this large review of 176 papers was to discuss the role of nutrients and genetics in NAFLD and heart disease. Amongst the main nutrients, excess fructose (a simple sugar) and high saturated and trans-fats were all shown to contribute to the development of both diseases. The influence of protein on NAFLD is controversial. Animal studies suggest that protein can be of benefit, but studies on humans have failed to support this. This is similar for heart disease where large scale trials in humans are not definitive. The role of fibre in NAFLD and heart disease appears to be beneficial. Several micronutrients were also reviewed including vitamins D, K, curcumin, plant chemicals and caffeine. The complex interplay involving genetics was also discussed and although fairly new science, evidence is mounting in support of genetic considerations when making dietary recommendations. It was concluded that diet and genetics influence the development of NAFLD, and heart disease and dietary recommendations need to reflect this. This study could be used by health care professionals to understand the interaction between diet and genetics and the importance of making personalised nutrition recommendations to individuals with NAFLD or heart disease.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage. Beyond genetic influence, also epigenetics modifications are responsible for various clinical manifestations of both hepatic and CV disease. Interestingly, data are accumulating on the interplay between diet and genetic and epigenetic modifications, modulating pathogenetic pathways in NAFLD and CV disease. We report the main evidence from literature on the influence of both macro and micronutrients in NAFLD and CV damage and the role of genetics either alone or combined with diet in increasing the risk of developing both diseases. Understanding the interaction between metabolic alterations, genetics and diet are essential to treat the diseases and tailoring nutritional therapy to control NAFLD and CV risk.
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Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability.
Mas-Capdevila, A, Teichenne, J, Domenech-Coca, C, Caimari, A, Del Bas, JM, Escoté, X, Crescenti, A
Nutrients. 2020;12(5)
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Cardiovascular diseases (CVDs) cause around 31% of all deaths worldwide. Certain dietary patterns have been associated with a reduction in CVDs and so the use of natural-based products has gained importance as a preventive strategy. Hesperidin is a bioactive compound found in high levels in citrus fruits. The reported beneficial properties include antitumor, antioxidant, anti-inflammatory; cholesterol and glucose lowering effects. Many animal studies show multiple beneficial effects but are inconclusive in human studies. The aim of this review is to describe the effects of hesperidin on CVD factors and to highlight the individual differences in its bioavailability and effectiveness. The gut bacteria play an important role in this. Hesperidin is not broken down by the normal digestive process and reaches the colon largely intact. It is the job of the gut bacteria to break it down into bioavailable substances that can be absorbed and utilised. The discrepancies observed in some of the results from human clinical trials may be partly due to individual differences, including that of the gut bacteria. Further clinical trials should be considered as well as classifying individuals according to individual differences in metabotypes.
Abstract
Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.
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Ketogenic diet in the treatment of cancer - Where do we stand?
Weber, DD, Aminzadeh-Gohari, S, Tulipan, J, Catalano, L, Feichtinger, RG, Kofler, B
Molecular metabolism. 2020;33:102-121
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A literature review paper looking at complementary approaches to improve the efficacy of standard anticancer therapies – specifically the Ketogenic Diet (KD), characterised as a high-fat (90%), low-carbohydrate (2%) diet with adequate amounts of protein (8%). The KD is a low- cost adjuvant to cancer therapy and is considered promising due to its potential to target metabolic alterations in tumour cells. Research shows it potentially limits tumour growth, whilst protecting healthy cells from damage by chemotherapy or radiation and reducing inflammation. The ketones produced by the high ratio of fat in the diet are used to create ATP energy, which cancerous cells are unable to use. Preclinical studies show that in most cases the KD slowed tumour growth, prolonged survival rate, and delayed the initiation of tumours although this may be influenced by cancer type and genetic background. This implies it’s important to evaluate KD efficiency against each individual cancer rather than as a collective anticancer therapy. Gold standard therapy for some cancers is surgery, radiation, and chemotherapy. However aggressive cancer types with poor prognosis need new approaches where standard therapy is less successful. The authors recognise there is insufficient RCT evidence with large patient cohorts but smaller studies are emerging showing positive results for a KD with patients exceeding their expected lifespan, with reduced tumour growth and progression, reduced glucose up-take at the tumour site and overall improved quality of life. KD seemingly creates an environment in which cancer cells cannot thrive making it a promising adjuvant as a patient-specific multifactorial therapy.
Abstract
BACKGROUND Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy. SCOPE OF REVIEW To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet. MAJOR CONCLUSIONS The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.
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Potential Adverse Effects of Resveratrol: A Literature Review.
Shaito, A, Posadino, AM, Younes, N, Hasan, H, Halabi, S, Alhababi, D, Al-Mohannadi, A, Abdel-Rahman, WM, Eid, AH, Nasrallah, GK, et al
International journal of molecular sciences. 2020;21(6)
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Resveratrol is a polyphenol compound found naturally in plant foods. It has several therapeutic effects including antioxidant, anti-inflammatory and cardio protective properties. This review focuses however on the potential adverse effects of resveratrol to better understand the nutrient and its use in therapy. Evidence suggests that dosage is important with low doses of resveratrol having beneficial effects, whilst high doses can be associated with toxicity. However, many studies also report poor bioavailability of resveratrol meaning the body is unable to absorb it efficiently. This may also be influenced by differences in gut bacteria. So, toxicity will differ from one patient to the next. It is also noted that most studies focus on short-term usage and outcomes whilst more data may be required to understand the effects of longer-term usage. The differences in studies, and usage of resveratrol, means the characteristics of patients and symptoms reported vary greatly. This makes it hard to rigorously evaluate adverse effects as there is a high level of variability between one study and another. The review concludes that if there was more uniformity in study designs it would be easier to evaluate both beneficial and adverse effects.
Abstract
Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects. In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.
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Alpha-Linolenic and Linoleic Fatty Acids in the Vegan Diet: Do They Require Dietary Reference Intake/Adequate Intake Special Consideration?
Burns-Whitmore, B, Froyen, E, Heskey, C, Parker, T, San Pablo, G
Nutrients. 2019;11(10)
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Fish and seafood are good sources of long-chain omega-3 fatty acids, like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A vegan diet does not include animal-sourced foods and is therefore void of EPA and DHA, unless algae-derived omega-3 supplements are consumed. Thus, vegans rely on the body's own production of long-chain fatty acids from plant-derived alpha-linolenic acid (ALA). However, adequate conversion can have several limitations. Vegan diets are generally rich in linoleic acid (LA), an omega-6 fatty acid, which in high levels can impede the conversion of ALA to EPA and DHA. Furthermore, the efficiency of conversion is influenced by gender, age or health conditions like obesity. This review sought to discuss whether vegans require special dietary recommendations for fatty acids and what these suggestions could be. Most studies assessing biological indicators of fatty acid status showed that vegans had lower levels of EPA and DHA compared to omnivores. Thus, the authors concluded that special consideration should be given to ALA and LA intake in vegan diets. In the absence of a set recommendation for a fatty acid ratio, a ratio of 4:1 (omega-6:omega-3) was proposed for vegans and omnivores. A reduction in LA and an increased intake of ALA of 2.2–4.4 g/day (or 1.1 g/day/1000 Kcals) was suggested to achieve such. This article is a useful guide when considering adequate fatty acid balance and omega-3 conversion for individuals following a vegan diet.
Abstract
Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.
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The Effects of Vegetarian and Vegan Diets on Gut Microbiota.
Tomova, A, Bukovsky, I, Rembert, E, Yonas, W, Alwarith, J, Barnard, ND, Kahleova, H
Frontiers in nutrition. 2019;6:47
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The difference in gut microbiota composition between individuals following vegan or vegetarian diets and those following omnivorous diets is well documented. A plant-based diet appears to be beneficial for human health by promoting the development of more diverse and stable microbial systems. This diversity appears to have an important association with BMI, obesity, and arterial compliance. This review highlights the effects of different diets, particularly plant-based diets, on the gut microbiota composition and production of microbial metabolites affecting the host health. The ratio between Bacteroidetes and Firmicutes is discussed and how different diets can change it. It explains how diet can affect the three main enterotypes: Prevotella, Bacteroides, and Ruminococcus. The food components proteins, carbohydrates, fats and polyphenols are discussed and how they influence gut microbiota. Up to date knowledge suggests that a plant-based diet may be an effective way to promote a diverse ecosystem of beneficial microbes that support overall health. However, due to the complexity and inter-individual differences, further research is required to fully characterize the interactions between diet, the microbiome, and health outcomes.
Abstract
The difference in gut microbiota composition between individuals following vegan or vegetarian diets and those following omnivorous diets is well documented. A plant-based diet appears to be beneficial for human health by promoting the development of more diverse and stable microbial systems. Additionally, vegans and vegetarians have significantly higher counts of certain Bacteroidetes-related operational taxonomic units compared to omnivores. Fibers (that is, non-digestible carbohydrates, found exclusively in plants) most consistently increase lactic acid bacteria, such as Ruminococcus, E. rectale, and Roseburia, and reduce Clostridium and Enterococcus species. Polyphenols, also abundant in plant foods, increase Bifidobacterium and Lactobacillus, which provide anti-pathogenic and anti-inflammatory effects and cardiovascular protection. High fiber intake also encourages the growth of species that ferment fiber into metabolites as short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. The positive health effects of SCFAs are myriad, including improved immunity against pathogens, blood-brain barrier integrity, provision of energy substrates, and regulation of critical functions of the intestine. In conclusion, the available literature suggests that a vegetarian/vegan diet is effective in promoting a diverse ecosystem of beneficial bacteria to support both human gut microbiome and overall health. This review will focus on effects of different diets and nutrient contents, particularly plant-based diets, on the gut microbiota composition and production of microbial metabolites affecting the host health.
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A Review of Dietary (Phyto)Nutrients for Glutathione Support.
Minich, DM, Brown, BI
Nutrients. 2019;11(9)
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Glutathione is made up of 3 amino acids (cysteine, glutamic acid and glycine) and plays important roles in the body, including oxidative stress reduction, supporting the immune system and contributing to detoxification processes. Evidence suggests that it is an important marker and target for treatment in many chronic, age-related diseases. This review article explores the evidence of nutritional strategies to improve glutathione status. The authors examine the evidence for supplementation of the precursors of glutathione as well as with various forms of supplemental glutathione itself, and the impacts on glutathione status and clinical impacts. Crucially, the review article provides information on dietary sources of precursors of glutathione and glutathione itself, which will provide Nutrition Practitioners with compelling information for use in clinic. Lean protein, brassica vegetables, polyphenol-rich fruits and vegetables, green tea, herbs and spices and omega-3 rich foods are all discussed in detail.
Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
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Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
Xie, C, Halegoua-DeMarzio, D
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an excessive accumulation of fat in the liver tissue, without excessive alcohol consumption, and appears to be related to metabolic syndrome. It is thought to have a prevalence of 25% globally and there are no pharmacological treatments available. This review discusses the connection between the gut microbiota (GM) and NAFLD. Various mechanisms by which the GM may be involved in the development of NAFLD are discussed. As probiotics and prebiotics can normalise GM and reverse dysbiosis their use may benefit patients with NAFLD. This has been confirmed in animal models. The authors review 26 randomised controlled trials (RCTs) of probiotics and/or prebiotics in the treatment of NAFLD which evaluate biochemical markers, as well as five meta-analyses, and found that overall there is strong evidence that probiotics and/or prebiotics can lower ALT and AST (markers of NAFLD), although results for other biochemical markers were mixed. They also reviewed RCTs assessing NAFLD by imaging and histological means, and again found benefits from probiotic and/or prebiotic supplementation.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.